Breast cancer is the second most frequently diagnosed cancer and the second cancer killer in U.S. women. Due to recent advances in medical imaging, efficient screening and early detection of breast cancer have resulted to lower morbidity from the disease. Because of the successful detection of breast cancer at an early stage, treatment techniques have also improved. The premise of ablation techniques is that, if a tumor and its normal-tissue margin can be destroyed in situ, instead of being removed, the impact on the disease should be equivalent. In addition, if the mortality associated with operative intervention can be avoided, then the outcome using localized treatments may be more advantageous. Ablation techniques are therefore slowly emerging as less invasive, but equally effective, in the treatment of early-stage breast cancer, with High-Intensity Focused Ultrasound (HIFU) being the only truly noninvasive, nonionizing, extracorporeal technique. HIFU has been applicable in the treatment of early-stage breast cancer with zero re-occurrence or skin damage (Huber et al. 2001;Hynynen et al. 2001). However, its translation to the clinic has been hindered in part by the extremely costly and slow monitoring MR-based methods used albeit their high image quality. Thus, there is currently a need for a simple, cost-efficient device that can reliably monitor HIFU treatment. In order to ensure its translation and reduce the cost of monitoring of HIFU monitoring while maintaining all its advantages, we have developed the radiation-force technique of Harmonic Motion Imaging (HMI) that can be used seamlessly in conjunction with HIFU for tumor ablation monitoring, namely HMI for Focused Ultrasound (HMIFU). HMIFU is thus an 1) entirely noninvasive (non-contact), 2) simple to implement, 3) real-time, 4) precise (estimating displacements of 1-10 microns), 5) fully integratable, and 6) low-cost technique for localized detection and in situ thermal treatment planning and monitoring of early-stage breast cancer. The general objective of the proposed study is to develop, optimize and test a real-time HMIFU system for tumor ablation and monitoring by utilizing the tumor's change in viscoelasticity property estimation during heating in phantom, ex vivo and in vivo murine and human applications. The underlying hypothesis is that the tumor and thermal lesion have sufficiently distinct mechanical properties compared to the normal tissue so that the system can treat and monitor the treatment of such a tumor. The specific aims of the proposed study are thus to: 1) implement an all ultrasound-based system for real-time thermal ablation generation and monitoring and test in phantom and post-surgical breast specimens;2) apply HMIFU and assess its performance in animal tumor models in vivo;and 3) demonstrate initial clinical feasibility in human subjects with breast cancer in vivo. In summary, HMIFU can constitute a simple, noninvasive, real-time and low-cost monitoring technique for benign or early-stage breast tumors. More importantly, it may prove to be an important option to women without limited, focal disease, for whom less invasive and more focal treatment is most beneficial with minimized mortality and risk. PUBLIC HEALTH RELEVANCE: An ultrasound-based, integrated system will be optimized for real-time localization and monitoring of tumor ablation in vivo. This will constitute a simple, low-cost, noninvasive and real-time method for simultaneous, fast and effective tumor detection and treatment. This new method may prove to be an important option offered to older women with early-stage breast tumors.